Journal of Hepatocellular Carcinoma最新文献

{"title":"Real-World Study of Post-Recurrence Treatment Strategies for Microvascular Invasion-Positive Hepatocellular Carcinoma After Curative Resection.","authors":"Xiao Liu, Xiaokun Chen, Ziyue Huang, Taifeng Zhu, Shunda Du","doi":"10.2147/JHC.S616238","DOIUrl":"https://doi.org/10.2147/JHC.S616238","url":null,"abstract":"<p><strong>Introduction: </strong>Optimal treatment for recurrent hepatocellular carcinoma (HCC) after curative resection remains unclear, particularly in patients with microvascular invasion (MVI). This study evaluated post-recurrence treatment patterns and survival outcomes in this population.</p><p><strong>Methods: </strong>We retrospectively included patients with MVI-positive HCC who developed recurrence after curative hepatectomy at a single center. Post-recurrence progression-free survival (PFS) was the primary endpoint and overall survival (OS) was the secondary endpoint. Kaplan-Meier analysis was used to compare survival across post-recurrence treatment groups. Cox regression, subgroup analysis, propensity score matching, and correlation analysis between recurrence-free survival (RFS) and post-recurrence PFS were also performed.</p><p><strong>Results: </strong>A total of 150 patients were included, and 132 received post-recurrence treatment. Treatment strategies were heterogeneous, with locoregional therapy plus tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI), surgery-based therapy, locoregional therapy plus TKI, and locoregional therapy alone being the main approaches. Median PFS and OS were 10.4 and 26.7 months, respectively. Survival outcomes differed across treatment groups in the unadjusted analysis. Patients receiving surgery-based therapy showed more favorable PFS and OS than those receiving locoregional therapy alone, although this finding should be interpreted cautiously given the non-randomized treatment allocation and potential baseline imbalances among treatment groups. In exploratory multivariable analysis, locoregional therapy plus TKI, locoregional therapy plus TKI and ICI, and surgery-based therapy were associated with longer PFS, whereas no treatment regimen was independently associated with OS. Among patients with potentially resectable recurrence, surgery-based therapy showed numerically more favorable outcomes before matching. However, the differences were not statistically significant and became less apparent after propensity score matching.</p><p><strong>Conclusion: </strong>Post-recurrence management in MVI-positive HCC after curative resection was highly heterogeneous. Surgery-based therapy was associated with favorable outcomes in selected patients, but this association may have been influenced by recurrence pattern and patient selection. Locoregional therapy combined with systemic treatment may be considered a clinically relevant option for non-surgical candidates, although its comparative effectiveness requires further validation.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"616238"},"PeriodicalIF":3.9,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13480360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transformer-Based Habitat Fusion Model Using DCE-MRI Predicts Microvascular Invasion and Recurrence in Hepatocellular Carcinoma.","authors":"Fei Jia, Baolin Wu, Jingqi Jiang, Zhuo Wang, Yuping Han, Jinrui Liu, Mingsong Tang, Xuelian Zhao, Yanli Jiang, Jing Zhang","doi":"10.2147/JHC.S615663","DOIUrl":"https://doi.org/10.2147/JHC.S615663","url":null,"abstract":"<p><strong>Background: </strong>Microvascular invasion (MVI) is the primary risk factor driving recurrence and metastasis of hepatocellular carcinoma (HCC) after surgical treatment. We developed a fusion model integrating dynamic contrast-enhanced MRI (DCE-MRI)-derived habitat radiomics and conventional radiomics with clinical features to preoperatively predict MVI status and recurrence-free survival (RFS).</p><p><strong>Methods: </strong>This study included 193 HCC patients from two centers. Logistic regression analysis was used to identify the independent clinical predictors of MVI. Additionally, habitat radiomics and conventional radiomics were derived from the DCE-MRI data. A transformer deep-learning model was used to integrate multimodal habitat features. Subsequently, a habitat model, a radiomics model and a clinical model were constructed. These models were then integrated into different fusion models. The performance of the single and fusion models was evaluated using different metrics, and the RFS was assessed using Kaplan-Meier analysis.</p><p><strong>Results: </strong>Multivariate analysis identified pseudocapsule integrity and tumor diameter as independent clinical predictors of MVI. Transformer outperformed traditional machine learning methods in fusing multimodal habitat features. A fusion model integrating habitat radiomics, conventional radiomics and clinical predictors demonstrated the best performance (training data: area under the curve [AUC] = 0.950, 95% confidence interval [CI]: 0.918-0.981; testing data: AUC = 0.923, 95% CI: 0.858-0.988) for predicting MVI, with robust calibration and satisfactory clinical utility. Kaplan-Meier analysis confirmed significant RFS stratification for both MVI-positive (<i>p</i> = 0.038) and high-risk nomogram groups (<i>p</i> = 0.033).</p><p><strong>Conclusion: </strong>A fusion model integrating DCE-MRI-based habitat radiomics and conventional radiomics with clinical features provides excellent prediction of MVI (AUC = 0.923) and RFS in patients with HCC. This model may provide important support for optimized surgical planning and personalized therapy.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"615663"},"PeriodicalIF":3.9,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13480390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neoadjuvant Hepatic Arterial Infusion Chemotherapy with FOLFOX Plus Tislelizumab for Resectable Hepatocellular Carcinoma Beyond the Milan Criteria: Efficacy, Safety and Biomarker Exploration.","authors":"Quanwei Dai, Huiting Deng, Jun Wang, Jingxiang Shi, Jianmin Ding, Yanying Gao, Wei Sun, Yunzhi Shen, Ximo Wang, Cheng Lou","doi":"10.2147/JHC.S615120","DOIUrl":"10.2147/JHC.S615120","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy of oxaliplatin, fluorouracil, and leucovorin (FOLFOX-HAIC) combined with tislelizumab as a neoadjuvant regimen in patients with resectable hepatocellular carcinoma (HCC) beyond the Milan criteria, and to explore predictive biomarkers of treatment response.</p><p><strong>Results: </strong>26 patients completed neoadjuvant therapy, with a median tumor size of 6.35cm. The objective response rate according to mRECIST criteria reached 57.7%, and the disease control rate was 96.2%. 22 patients underwent radical surgery, and 10 patients (10/22, 45.5%) achieved major pathological response (residual viable tumor ≤10%). Six patients (27.3%) achieved complete pathological response, and 25 patients (96.2%) experienced at least one treatment-related adverse events (TRAEs) The most common TRAEs were elevated transaminases (76.9%), HAIC-related pain (34.6%). Transcriptomic analysis revealed that differential genes between responding and non-responding tumors primarily involved pathways related to bile acid secretion and fatty acid metabolism. Metabolomic analysis showed elevated serum chenodeoxycholic acid (CDCA) in non-responders and elevated tumor glycocholic acid (GCA). Microbiome analysis further confirmed increased abundance of bile acid metabolism-related bacteria such as bacteroides in non-responders. Serum interleukin-6 (IL-6) levels after neoadjuvant therapy were correlated with treatment response.</p><p><strong>Conclusion: </strong>FOLFOX-HAIC combined with tislelizumab as neoadjuvant therapy for HCC beyond the Milan criteria demonstrates favorable anti-tumor efficacy and controllable toxicity. The level of GCA in tumor, peripheral blood CDCA, IL-6, and fecal bacteroides may hold the potential to serve as a composite biomarker panel to predict pathological response and treatment sensitivity.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"615120"},"PeriodicalIF":3.9,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13477671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction and Validation of a Risk Prediction Model for Postoperative Nausea and Vomiting in Patients with Liver Cancer.","authors":"Dandan Geng, Jun Wang, Yan Zhu, Jin Gao, Yuxia Zhang, Xiao Chen, Jingxian Yu","doi":"10.2147/JHC.S610768","DOIUrl":"https://doi.org/10.2147/JHC.S610768","url":null,"abstract":"<p><strong>Background: </strong>Postoperative nausea and vomiting (PONV) is a common and distressing complication following liver cancer surgery. This study aimed to develop and validate a risk prediction model for PONV in patients undergoing hepatectomy for hepatocellular carcinoma.</p><p><strong>Methods: </strong>This prospective study enrolled patients who underwent liver resection between February 2024 and December 2024. Based on risk factors identified through univariate and binary logistic regression analyses, a nomogram prediction model was constructed. The model's discrimination was evaluated using the area under the receiver operating characteristic curve (AUC-ROC) and the consistency index (C-index). Calibration was assessed with calibration curves, and internal validation was performed via the bootstrap method.</p><p><strong>Results: </strong>A total of 512 patients were included in the modeling cohort. The incidence of PONV was 47.5%. Significant predictors incorporated into the nomogram included age, gender, duration of surgery (min), time of hepatic portal vein occlusion during operation (min), and history of PONV. The model demonstrated an AUC of 0.717 (95% CI: 0.673-0.761), with a sensitivity of 69.9% and a specificity of 62.0% at the optimal cut-off value of 0.413. Bootstrap internal validation yielded a C-index of 0.717, and the calibration curve indicated good agreement between predicted and observed outcomes.</p><p><strong>Conclusion: </strong>The developed risk warning model shows an acceptable predictive effect in identifying the risk of PONV in patients with liver cancer. It can assist clinical medical staff in early risk assessment and individualized intervention, and has certain predictive value.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"610768"},"PeriodicalIF":3.9,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13478232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Changes in the Neutrophil-to-Lymphocyte Ratio are Associated with Conversion Outcomes in Advanced Hepatocellular Carcinoma Treated with HAIC-Based Triple Therapy.","authors":"Yang Wang, Xiaoyi Duan, Huanzhang Niu, Chaoyang Wang","doi":"10.2147/JHC.S625619","DOIUrl":"https://doi.org/10.2147/JHC.S625619","url":null,"abstract":"<p><strong>Background: </strong>Reliable early biomarkers for identifying conversion potential during HAIC-based triple therapy in advanced unresectable hepatocellular carcinoma (uHCC) remain lacking. This study evaluated the predictive value of dynamic systemic inflammatory remodeling during treatment.</p><p><strong>Methods: </strong>In this single-center retrospective cohort study, we included 296 patients with advanced uHCC treated with hepatic artery infusion chemotherapy combined with tyrosine kinase inhibitors and immune checkpoint inhibitors. Patients were stratified according to conversion status. ΔNLR was calculated as the NLR measured after the first treatment cycle minus the baseline NLR. Predictors for conversion were identified using logistic regression and evaluated via receiver operating characteristic analysis. A predictive nomogram was subsequently constructed and validated using calibration and decision curve analyses.</p><p><strong>Results: </strong>Among 296 patients, 125 (42.2%) achieved successful conversion resection. Baseline NLR showed minimal predictive value for conversion (AUC = 0.501), whereas ΔNLR demonstrated significantly improved predictive performance (AUC = 0.819). The optimal cohort-derived cutoff was ΔNLR ≤ 0.20, with a sensitivity of 72.0% and a specificity of 91.8%. Multivariate analysis showed that higher ΔNLR was independently associated with lower odds of successful conversion (OR = 0.415, 95% CI: 0.328-0.524, P < 0.001). Patients in the conversion group achieved significantly improved tumor responses, overall survival, and progression-free survival. The nomogram incorporating ΔNLR demonstrated good calibration and clinical utility.</p><p><strong>Conclusion: </strong>Lower ΔNLR values after one treatment cycle were associated with successful conversion resection during HAIC-based triple therapy for advanced uHCC. ΔNLR may serve as a candidate early marker of conversion potential, pending prospective external validation.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"625619"},"PeriodicalIF":3.9,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13475547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential Prognostic Impacts of Hepatic Segment VI and VII Involvement in Hepatocellular Carcinoma.","authors":"Runze Yu, Zhiwen Luo, Hong Zhao, Jianjun Zhao","doi":"10.2147/JHC.S611036","DOIUrl":"10.2147/JHC.S611036","url":null,"abstract":"<p><p>This study aimed to investigate the impact of hepatic segment distribution on the prognosis of patients with primary hepatocellular carcinoma (HCC). A retrospective analysis was conducted on 456 eligible patients with primary HCC admitted to the Hepatobiliary Surgery Department of Cancer Hospital, Chinese Academy of Medical Sciences, from January 2013 to December 2017. Tumor hepatic segment location was confirmed by postoperative pathology or imaging examinations, and clinical data (e.g. age, surgical method, operation time) were collected from the HIS electronic medical record system. Follow-up ended on May 5, 2019, with overall survival (OS) as the primary endpoint. Results showed that most tumors (70.39%, 321/456) were located in the right hemi-liver, with the highest incidence in Segment VI (53.73%, 245/456) and Segment VII (46.05%, 210/456). Univariate analysis identified tumor diameter, tumor characteristics, surgical method, operation time, intraoperative blood loss, and hepatic segment location as factors associated with OS. Multivariate COX analysis revealed that tumor diameter, open surgery, and intraoperative blood loss were independent predictors of poor long-term prognosis. Notably, hepatic segment location exerted contrasting effects: Segment VI tumors independently associated with poorer prognosis (HR=2.04, 95% CI=1.11-3.74, p=0.021), while Segment VII tumors served as a significant survival benefit (HR=0.47, 95% CI=0.25-0.88, p=0.018). Further subgroup analysis indicated that the protective effect of Segment VII was more pronounced in tumors ≥6 cm (p=0.03), whereas for tumors <6 cm, Segment VII involvement had no significant prognostic impact (p=0.32). For Segment VI tumors, laparotomy was associated with poorer prognosis regardless of tumor size (<6 cm: p=0.029; ≥6 cm: p=0.039), a trend not observed in non-Segment VI tumors ≥6 cm (p=0.9). Hepatic segment distribution is an independent prognostic indicator and may serve as a surrogate marker reflecting tumor biology, surgical complexity, and treatment selection, rather than an independent causal determinant, with Segment VI and VII showing distinct prognostic roles: Segment VI involvement is associated with worse survival, while Segment VII involvement confers a survival benefit. These findings provide valuable insights for precision surgical decision-making in HCC, such as prioritizing minimally invasive approaches or neoadjuvant therapy for Segment VI tumors and considering de-escalated treatment for large Segment VII tumors. Future studies should explore the molecular and immune mechanisms underlying these segment-specific differences and validate the results through multicenter prospective trials.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"611036"},"PeriodicalIF":3.9,"publicationDate":"2026-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HAIC-Based Combination Therapy for Advanced Hepatocellular Carcinoma with Vp4 Portal Vein Tumor Thrombus and Child-Pugh B Liver Function: A Case Report.","authors":"Pan Xiao, Ke-Xin Chen, Li Zhang, Lian-Dong Shi, You-Fu Bin","doi":"10.2147/JHC.S630938","DOIUrl":"10.2147/JHC.S630938","url":null,"abstract":"<p><p>Advanced hepatocellular carcinoma (HCC) with Vp4/main portal vein tumor thrombus (PVTT) and Child-Pugh B liver function remains difficult to manage because patients with impaired hepatic reserve are vulnerable to hepatic decompensation and are underrepresented in pivotal systemic therapy trials. We report a 57-year-old man with hepatitis B virus-related cirrhosis, advanced HCC, Vp4 PVTT, BCLC stage C/CNLC stage IIIa disease, Child-Pugh B7 liver function, and ECOG performance status 1. Baseline contrast-enhanced computed tomography (CT) showed multifocal confluent intrahepatic tumors forming a measurable target mass of 91 mm × 71 mm. After multidisciplinary evaluation, the patient received modified FOLFOX-based hepatic arterial infusion chemotherapy (HAIC) every 3 weeks for four cycles, combined with lenvatinib (8 mg once daily), camrelizumab (200 mg every 3 weeks), and entecavir. After four cycles, the confluent target lesion decreased to 46 mm × 45 mm, alpha-fetoprotein (AFP) decreased from 656 ng/mL to 3.58 ng/mL (normal range, 0-7 ng/mL), and PVTT burden decreased radiologically. Ascites present at baseline resolved during treatment. At 34 months, the residual lesion measured 41 mm × 28 mm, AFP remained within the normal range, no new intrahepatic lesions were detected, and PVTT remained controlled, although a small amount of ascites was again detected. A retrospective RECIST version 1.1 assessment classified the best overall response as partial response, which was sustained at the 34-month follow-up. The Child-Pugh score was B7 at baseline, improved to A5 after ascites resolution, and was A6 at the 34-month follow-up. No grade 3 or higher treatment-related adverse events were documented. This case does not establish treatment efficacy but illustrates a hypothesis-generating approach to patient selection, non-embolization-based locoregional therapy, antiviral treatment, and longitudinal safety monitoring in a high-risk HCC subgroup for whom prospective evidence is limited.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"630938"},"PeriodicalIF":3.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline ALBI Grade as an Independent Prognostic Factor of Survival in High-Risk Real-World HCC Under Atezolizumab-Bevacizumab.","authors":"Filiz Araz, Fatih Köse, Timuçin Çil, Berna Bozkurt Duman, Burcu Arslan Benli, Elif Karadeli, Okan Dilek","doi":"10.2147/JHC.S617103","DOIUrl":"10.2147/JHC.S617103","url":null,"abstract":"<p><strong>Background/aim: </strong>Atezolizumab plus bevacizumab is the current first-line standard for unresectable hepatocellular carcinoma (HCC). However, real-world populations often differ substantially from clinical trials particularly in terms of hepatic reserve and tumor burden. We aimed to evaluate survival outcomes and hepatic functional changes in a real-world cohort, specifically focusing on the prognostic role of baseline ALBI grade and portal vein tumor thrombosis (PVTT).</p><p><strong>Methods: </strong>This multicenter retrospective cohort study analyzed 43 patients with BCLC-B/C unresectable HCC treated between January 2022 and June 2025. Tumor response was assessed according to mRECIST. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Cox regression analyses were performed to identify independent prognostic factors.</p><p><strong>Results: </strong>The cohort was characterized by advanced disease (72.1% BCLC-C stage, 74.5% ALBI grade ≥2, and 41.9% PVTT). Median OS and PFS were 9.5 months (95% CI, 6.5-12.4) and 6 months (95% CI, 3.8-8.2), respectively. Patients with ALBI grade 1 had significantly longer OS compared to those with ALBI ≥2 (21 vs 8 months; p=0.018). In multivariable Cox regression analysis, higher baseline ALBI grade was independently associated with shorter OS (HR 3.1, 95% CI 1.1-8.3; p=0.027) and PFS (HR 2.8, 95% CI 1.2-6.9; p=0.021). Hepatic decompensation occurred in 41.9% of patients and was associated with deterioration in liver function scores.</p><p><strong>Conclusion: </strong>In this high-risk real-world cohort of patients with HCC treated with atezolizumab plus bevacizumab, baseline ALBI grade was independently associated with poorer survival outcomes, suggesting that hepatic functional reserve may be important for prognostic stratification. Larger prospective studies are needed to clarify the relative prognostic contributions of ALBI grade and tumor-related factors such as PVTT.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"617103"},"PeriodicalIF":3.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Single‑Center Retrospective Cohort Study: Impact of Glycemic Control on First‑Line TKI Plus PD‑1 Inhibitors versus TKI Alone in Intermediate‑to‑advanced Unresectable Hepatocellular Carcinoma(HCC) with Type 2 Diabetes Mellitus (T2DM).","authors":"Jiaqi Liu, Xiong Chen, Runxian Wang, Caiyun Peng, Hongli Yu, Wenjing Wang, Weihong Ma, Jie Han, Zhipeng Liang, Yunqiao Yang, Jiamin Cheng, Yinying Lu","doi":"10.2147/JHC.S619596","DOIUrl":"10.2147/JHC.S619596","url":null,"abstract":"<p><strong>Background and aim: </strong>Type 2 diabetes mellitus (T2DM) is an independent risk factor for hepatocellular carcinoma (HCC), and the number of HCC patients with comorbid T2DM is increasing. Although tyrosine kinase inhibitor (TKI) monotherapy or combination with programmed death‑1 (PD‑1) inhibitors has become the first‑line standard of care for advanced HCC, most relevant clinical trials excluded patients with poorly controlled glycemia. Consequently, direct comparisons of efficacy and safety between first‑line regimens specifically in T2DM‑combined HCC populations remain insufficiently explored, and the impact of glycemic control on treatment outcomes also remains unclear. Therefore, this study retrospectively compares first‑line TKI monotherapy versus combined regimens in this population, with a focus on the effect of glycemic control status on prognosis, and aims to construct a prognostic nomogram integrating clinical and metabolic indicators to support individualized risk assessment.</p><p><strong>Methods: </strong>We retrospectively analyzed HCC patients with T2DM who received TKI monotherapy or TKI+PD-1 between January 2019 and January 2024. Overall survival (OS) and progression‑free survival (PFS) was analyzed using Cox regression (HR). Cancer‑specific death (with non‑cancer death as competing event) and PFS were evaluated using Fine‑Gray competing risk models (sHR). A prognostic nomogram incorporating independent predictors was developed and internally validated.</p><p><strong>Results: </strong>A total of 374 patients were enrolled (217 TKI+PD-1, 157 TKI), with 135 per group after Propensity Score Matching (PSM) (1:1). Post-PSM, the TKI group showed significantly inferior median OS (mOS: 20.7 months vs 26.8 months, HR=2.009, 95% CI 1.438-2.807, P<0.001) and PFS (mPFS: 11 months vs 16 months, HR=2.086, 95% CI 1.495-2.911; All P<0.001) compared to the TKI+PD-1 group. In the TKI cohort, poor glycemic control was associated with significantly worse OS (HR=2.125, 95% CI 1.215-3.714, P<0.001) and PFS (HR=2.210, 95% CI 1.292-3.781, P<0.001), but this association was not observed in the TKI+PD-1 cohort. The prognostic nomogram (corrected C index = 0.652) showed acceptable calibration and provided modest stratification patients into three risk groups (median OS: 19.3, 16.5 and 13.8 months, log rank P<0.001). Grade 1-2 diarrhea was lower in the TKI+PD-1 group (16.6% vs 26.8%, <i>P</i> = 0.017), with no increase in high-grade adverse events.</p><p><strong>Conclusion: </strong>In HCC patients with T2DM, TKI+PD-1 offers superior OS and PFS compared to TKI alone. Glycemic control significantly impacts prognosis in patients receiving TKI monotherapy but its independent effect is diminished in those on combination immunotherapy. The proposed nomogram provides an individualized prognostic tool for this patient population.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"619596"},"PeriodicalIF":3.9,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13453368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PTM-Related Signatures Predict Lymph Node Metastasis and Shape Microenvironment in Hepatocellular Carcinoma: A Single-Cell and Bulk Integrated Analysis.","authors":"Zhu Ai, Yuying Liang, Yuzhi Cai, Jian Gao, Lin Ren, Qiong Wang, Yutong Chen, Yongye Huang, Zhiming Xiang","doi":"10.2147/JHC.S607916","DOIUrl":"10.2147/JHC.S607916","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) has a poor prognosis with lymph node metastasis (LNM), severely impacting survival. Protein post-translational modifications (PTMs) regulate tumor microenvironment (TME) dynamics, but their role in HCC LNM is unknown.</p><p><strong>Methods: </strong>This study systematically analyzed single-cell RNA sequencing (scRNA-seq) and bulk transcriptomic data from TCGA-LIHC and validation cohorts. Key cellular subpopulations and differentially expressed genes (DEGs) were identified. PTM-related candidate genes were identified through intersection analysis. Prognostic genes were determined via Cox regression and integrated into a random survival forest (RSF) model. Patients were stratified to assess associations with TME remodeling, genomic alterations, immune checkpoints, and drug sensitivity. Pseudotime trajectory and transcription factor activity analyses elucidated molecular dynamics.</p><p><strong>Results: </strong>Hepatocyte populations were significantly expanded in both LNM and non-LNM HCC groups. The intersection of scRNA-seq DEGs, bulk DEGs, and PTM-related genes identified five candidate genes, among which PJA1 and RFPL4B identified as potential prognostic risk factors and were incorporated into a robust RSF model. High-risk patients exhibited poor survival outcomes, increased tumor mutational burden, and pronounced tumor microenvironment alterations. PJA1 expression was negatively correlated with hepatocyte infiltration. Pseudotime analysis revealed that LNM-associated hepatocytes were arrested in early differentiation states, coinciding with dysregulated transcription factor activity.</p><p><strong>Conclusion: </strong>This study computationally identified PJA1 and RFPL4B as post-translational modification-related candidate prognostic genes potentially associated with HCC LNM. The proposed risk model stratified patients into subgroups characterized by distinct tumor microenvironment features and genomic instability. Computational analysis suggested that arrest of hepatocyte differentiation and dysregulation of transcription factor networks may be implicated in metastatic progression, thereby offering novel therapeutic insights.</p>","PeriodicalId":15906,"journal":{"name":"Journal of Hepatocellular Carcinoma","volume":"13 ","pages":"607916"},"PeriodicalIF":3.9,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}